The present application is generally directed to separating particles used in scientific procedures. In the past, laboratories have used centrifuges to separate target materials based on mass and/or filtration systems to separate them based on size. While these separation methods worked well in some cases, they were not suitable for high throughput testing required in biotechnology and other fields as they were time consuming and complex in their implementation. A third approach to separation uses magnetic flux to separate these target materials by way of specially formulated magnetic particles.
Small particles having either magnetic or paramagnetic qualities are used by a growing number of laboratories to perform separation in experiments and procedures. Unlike the purely magnetic particles, the paramagnetic type particles are responsive to magnetic and electromagnetic fields yet tend not to retain magnetic qualities outside the presence of these fields. This allows particles to be manipulated by magnetic fields yet not suffer from packing and particle aggregation over time. For purposes of discussion, reference to particles includes those considered magnetic, paramagnetic as well as super-paramagnetic.
The particles are typically sphere-like in shape and due to the nanometer radii they possess are particularly useful in nanotechnology and biotechnology applications. While these sphere-like particles are the most prevalent, the shape and size of the particle may vary depending on the experiment being performed and the particles available or suitable for the experiment or procedure. Consequently, a wide range of particle sizes are being manufactured to accommodate the various types of experiments and procedures.
In one implementation, particles are functionalized through a coating of magnetite or other magnetically responsive material along with potentially one or more recognition molecules or substances to be used in a particular experiment. The core of these magnetically coated particles can be non-magnetic if desired. Alternatively, the functionalized particles can include a magnetic core while the coating is of a non-magnetic material such as gold (Au).
The recognition molecule on the particle reacts with and captures a target in a given sample. Magnets attract the particles along with the target in the given sample while the unbound non-reactive portion of the sample is washed away or collected for other subsequent procedures. For example, functionalized magnetic microspheres have been used in Polymerase Chain Reaction (PCR) related procedures to accurately manipulate small sample sizes and otherwise help reduce the time spent performing experimental and often complex procedures.
To maintain consistent and reliable results in the laboratory, it is important that the particles are extremely close in size. Manufacturers are therefore required to create particles that are close in size or fit within a small range or degree of tolerance. Unfortunately, obtaining particle uniformity during manufacture is very time consuming and greatly increases costs. As a second measure, manufacturers have attempted to separate the particles by size using filtration thus ensuring the particles are no larger than a predetermined upper threshold. Additional techniques met with limited success have employed kinetic-magnetic washing to further refine the particle size into more specific categories. Once again, this latter methodology is time consuming and difficult to produce consistent results.
Laboratories need particles that are extremely close in size yet cost-effective for use in large-scale ongoing and automated experiments. For example, even particles described as ranging several microns in size with a small percentage of variability may not be sufficient for certain laboratories to use if reliable experimental and procedural results are expected. As much as possible, these particles need to be identified by their size and not just a threshold size they are alleged not to exceed.